DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor. (Articolo in rivista)

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  • DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor. (Articolo in rivista) (literal)
Anno
  • 2005-01-01T00:00:00+01:00 (literal)
Alternative label
  • Mazzarelli P., Parrella P., Seripa D., Signori E., Perrone G., Rabitti C., Borzomati D., Gabbrielli A., Matera M.G., Gravina C., Caricato M., Poeta M.L., Rinaldi M., Valeri S., Coppola R., Fazio V.M.. (2005)
    DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor.
    in World Journal of Gastroenterology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Mazzarelli P., Parrella P., Seripa D., Signori E., Perrone G., Rabitti C., Borzomati D., Gabbrielli A., Matera M.G., Gravina C., Caricato M., Poeta M.L., Rinaldi M., Valeri S., Coppola R., Fazio V.M.. (literal)
Pagina inizio
  • 6694 (literal)
Pagina fine
  • 6700 (literal)
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  • 11/42 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
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  • Paola Mazzarelli, Emanuela Signori, Maria Luana Poeta, Vito Michele Fazio, Laboratory of Molecular Medicine and Biotechnology, Interdisciplinary Center for Biomedical Research, Università Campus Bio-Medico, Rome 00155, Italy; Paola Parrella, Davide Seripa, Maria Giovanna Matera, Carolina Gravina, Vito Michele Fazio, Laboratory of Gene Therapy and Oncology, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG) 71013, Italy; Giuseppe Perrone, Carla Rabitti, Service of Histopathology, Università Campus Bio-Medico, Rome 00155, Italy; Domenico Borzomati, Marco Caricato, Sergio Valeri, Roberto Coppola, Department of General Surgery, Università Campus Bio-Medico, Rome 00155, Italy; Armando Gabbrielli, Department of Digestive Disease, Università Campus Bio-Medico, Rome 00155, Italy; Emanuela Signori, Monica Rinaldi, Vito Michele Fazio, CNR Gene-Medicine Division, Section of Molecular Medicine, Institute of Neurobiology and Molecular Medicine, Rome 00133, Italy; (literal)
Titolo
  • DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor. (literal)
Abstract
  • AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis. METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis. RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P<0.00). However, changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity. Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86 nuclear expression, as determined by Western blot and immunohistochemical analyses (P<0.001). Cytoplasmic protein expression was found in pathological samples, but not in normal tissues either from tumor patients or from healthy subjects. CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis. (literal)
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